Patients with Adult Respiratory Distress Syndrome (ARDS) exhibit a reduced ability to extract oxygen in peripheral tissues. Despite a normal or increased oxygen delivery to the periphery (cardiac output X arterial O2 content exceeds 15 ml/min/kg body wt.), whole body oxygen uptake (VO2) becomes limited by delivery when tissues have extracted only 30-40% of the oxygen available in blood. By contrast, critically ill patients without ARDS can maintain VO2 independent of O2 supply until delivery is reduced to a critically low level (8 ml/min/kg) where arteriovenous O2 extraction approaches 70%. Thus, the O2 uptake in patients with ARDS may be limited by an inability to extract sufficient O2 to meet metabolic needs. Proposed studies will clarify normal physiological mechanisms influencing the degree to which O2 extraction can increase before O2 supply dependence sets in. Other studies will clarify the mechanisms responsible for the abnormal O2 supply dependence observed in a canine model of bacterial sepsis. Additional studies will clarify the mechanisms and tissues responsible for an abnormal O2 extraction observed during ventilation with 100% oxygen. Finally, studies will explore specific models of tissue injury that may lead to an abnormal O2 supply dependence. Oxygen extraction ability will be assessed by gradually lowering oxygen delivery to estimate the lowest delivery and highest extraction achieved prior to the onset of supply limitation. Simultaneous measurements of O2 delivery and extraction will be made in whole body and isolated autoperfused hind limb, intestine and heart. Proposed measurements will quantify the relative contributions of a reduced extraction ability within tissues versus a supply dependency that results from a maldistribution of a limited O2 delivery among organ systems. Within tissues, measurements of permeability surface area products will clarify the relationship between capillary recruitment and the onset of normal or pathological O2 supply dependence. These studies will add to our understanding of the mechanisms influencing the degree to which normal and diseased tissues can extract oxygen to maintain a desired metabolic activity. They may also identify therapeutic interventions which can help to maintain extraction efficiency in patients with ARDS.